Evidence map›Paper›PMID 34949722›Full record

ArticleRNA (New York, N.Y.)2022

RNA uridyl transferases TUT4/7 differentially regulate miRNA variants depending on the cancer cell type.

Ragini Medhi, Jonathan Price, Giulia Furlan, Beronia Gorges, Alexandra Sapetschnig, Eric A Miska

Open access · hybridAbstract read
In one paragraph

Article in RNA (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.1field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 15 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Ragini MedhiDepartment of Genetics, University of Cambridge, Cambridge CB2 3EH, United Kingdom.
Jonathan PriceWellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom.
Giulia FurlanWellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, United Kingdom.
Beronia GorgesSTORM Therapeutics Limited, Moneta Building, Babraham Research Campus, Cambridge CB22 3AT, United Kingdom.
Alexandra SapetschnigSTORM Therapeutics Limited, Moneta Building, Babraham Research Campus, Cambridge CB22 3AT, United Kingdom.
Eric A MiskaDepartment of Genetics, University of Cambridge, Cambridge CB2 3EH, United Kingdom.ORCID 0000-0002-4450-576X
University of Cambridge · GBMission Therapeutics (United Kingdom) · GB

Funding

Cancer Research UK 18583Cancer Research UK 27826Cancer Research UK A24843Cancer Research UK C13474/A18583Cancer Research UK C6946/A14492Wellcome Trust 092096Wellcome Trust 092096/Z/10/ZWellcome Trust 203144Wellcome Trust 219475Wellcome Trust 219475/Z/19/Z
6 · The paper itself

Abstract

The human terminal uridyl transferases TUT4 and TUT7 (TUT4/7) catalyze the additions of uridines at the 3' end of RNAs, including the precursors of the tumor suppressor miRNA let-7 upon recruitment by the oncoprotein LIN28A. As a consequence, let-7 family miRNAs are down-regulated. Disruption of this TUT4/7 activity inhibits tumorigenesis. Hence, targeting TUT4/7 could be a potential anticancer therapy. In this study, we investigate TUT4/7-mediated RNA regulation in two cancer cell lines by establishing catalytic knockout models. Upon TUT4/7 mutation, we observe a significant reduction in miRNA uridylation, which results in defects in cancer cell properties such as cell proliferation and migration. With the loss of TUT4/7-mediated miRNA uridylation, the uridylated miRNA variants are replaced by adenylated isomiRs. Changes in miRNA modification profiles are accompanied by deregulation of expression levels in specific cases. Unlike let-7s, most miRNAs do not depend on LIN28A for TUT4/7-mediated regulation. Additionally, we identify TUT4/7-regulated cell-type-specific miRNA clusters and deregulation in their corresponding mRNA targets. Expression levels of miR-200c-3p and miR-141-3p are regulated by TUT4/7 in a cancer cell-type-specific manner. Subsequently, BCL2, which is a well-established target of miR-200c is up-regulated. Therefore, TUT4/7 loss causes deregulation of miRNA-mRNA networks in a cell-type-specific manner. Understanding of the underlying biology of such cell-type-specific deregulation will be an important aspect of targeting TUT4/7 for potential cancer therapies.

Indexed as

Gene Expression Regulation, NeoplasticCell Line, TumorDNA-Binding ProteinsHEK293 CellsHumansMicroRNAsNeoplasmsRNA NucleotidyltransferasesRNA Processing, Post-TranscriptionalDNA-Binding ProteinsMicroRNAsRNA NucleotidyltransferasesTUT4 protein, humanTUT7 protein, humancancerisomiRslet-7LIN28AmiRNA–mRNATUT4/7

Identifiers

PMID34949722
PMCPMC8848932
OpenAlexW4220920348

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.